A STUDY OF THE SYNERGISM BETWEEN METABOTROPIC GLUTAMATE-RECEPTOR ACTIVATION AND ARACHIDONIC-ACID IN THE RAT HIPPOCAMPUS

WE report that activation of the metabotropic glutamate receptor by th e specific agonist, trans-1-amino-cyclopentyl-1,3-dicarboxylate (ACPD) , increases release of glutamate only in the presence of a low concent ration of arachidonic acid (AA). To identify the molecular mechanism u nderlying this effect, cAMP accumulation, inositol phospholipid metabo lism and protein kinase C (PKC) activation were examined in synaptosom es prepared from hippocampus. ACPD increased cAMP accumulation, but th is increase was not further enhanced in the presence of AA. ACPD and A A stimulated both inositol phospholipid turnover and PKC activity; a s ynergistic action was indicated by the additional stimulation in the p resence of both agents. The increase in PKC activity, either directly, or indirectly by increased inositol phospholipid turnover, might ther efore underlie the enhanced glutamate release.